乌鸦传媒

Obesity has been linked to greater risk of cardiovascular disease (CVD) and death. A subgroup of individuals, however, have what is known as metabolically healthy obesity (MHO), which is purported to have no increased risk, compared to patients with metabolically unhealthy obesity (MUHO), who are at increased risk of adverse outcomes.^1,2

However, though it could be theorized that metabolically healthy obese individuals would therefore be at similar risk to normal weight metabolically healthy individuals, large studies and meta-analyses have instead shown a consistently increased risk of CVD and mortality in those with MHO when compared to metabolically healthy normal weight individuals, despite the absence of metabolic syndrome.^3-7 The investigators of a newly published study aimed at empirically defining MHO to allow for easier identification of this lower-risk subset of obese individuals.⁷

Rather than using stricter parameters for defining metabolic health, the investigators sought instead to define metabolic health (MH) in the context of risk factors for CVD and mortality among people with obesity.⁷ Mortality data on 12,341 patients with a mean of 14.5 years of follow-up in the third National Health and Nutrition Examination Survey (NHANES-III; mean [SD] age 41.6 [29.2] years, 50.7% women) were compared to CVD and mortality data from 374,079 individuals during a mean of 7.8 years of follow-up in the independent UK Biobank population-based prospective study (mean (SD) age was 56.2 [8.1] years, 55.1% women).⁷

Three BMI groups were used to compare patients鈥攏ormal weight (18.5-24.9), overweight (25.0-29.9), and obesity (鈮�30.0).⁷ Anthropometric and blood pressure (BP) measurements were conducted comparably in both cohorts using a representative complex multistage probability sampling where parameters associated with total and CVD mortality were determined by Cox proportional hazard regression models.⁷ Triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose, and hemoglobin A1c levels also were measured in both cohorts, while C-reactive protein, insulin, 纬-glutamyltransferase, and alanine aminotransferase levels were measured in the NHANES-III cohort.⁷ Self-reporting was used to determine race/ethnicity and prevalent diabetes in both cohorts.⁷ The UK Biobank also used self-report to determine current medications, while pill containers were presented at the interview in NHANES-III.⁷ Results from the two cohorts were compared with commonly used a priori definitions in both cohorts.⁷

CVD mortality and total mortality both were associated with the use of blood pressure (BP)-lowering medication (hazard ratio [HR] for CVD mortality, 2.41; 95% CI, 1.50鈥�3.87 and total mortality, 2.05; 95% CI, 1.47鈥�2.84).⁷ In addition, diabetes and several continuous factors were associated with mortality.⁷ The combination of systolic BP (SBP) and waist-to-hip ratio showed the highest area under the receiver operating characteristic of all significant continuous factors (CVD mortality: 0.77; 95% CI, 0.77鈥�0.78; total mortality: 0.696; 95% CI, 0.694鈥�0.699).

Based on these findings, MH was defined as SBP <130 mm Hg, no BP-lowering medication, waist-to-hip ratio <0.95 for women and <1.03 for men, and no self-reported diabetes.⁷ Overall, there was no association between MHO and CVD and total mortality compared with MH normal weight in either cohort.⁷ For NHANES-III and UK Biobank, respectively, the HRs were 0.68 (95% CI, 0.30鈥�1.54) and 1.17 (95% CI, 0.81鈥�1.69) for CVD mortality; and the HRs were 1.03 (95% CI, 0.70鈥�1.51) and 0.98 (95% CI, 0.87鈥�1.10) for total mortality.⁷

All MU groups displayed increased risks regardless of BMI.⁷

鈥淭he novel definition seems to allow [us] to identify a subgroup of obese [individuals] which has similar mortality risk compared to healthy normal-weight individuals,鈥� says the study鈥檚 senior investigator, Matthias B. Schulze, DrPH, department of molecular epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 鈥淧revious definitions of metabolic healthy obesity were not able to identify such a low-risk group (risk was still increased).鈥�

Schulze says additional outcomes need to be studied in those with MHO. 鈥淚t remains unclear if this low-risk status also applies to other obesity-related health outcomes, eg, type 2 diabetes, non-fatal cardiovascular events, etc,鈥� he says. 鈥淎lso, as it has been shown that a 鈥榟ealthy鈥� status may be a transient status for many (a large proportion of metabolically healthy obese has been observed to shift to an unhealthy status over time in previous studies), the long-term status would be interesting to evaluate.鈥�

Published: November 11, 2021